P496: CLINICAL CHARACTERISTICS OF SECONDARY MYELOID NEOPLASMS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: T. Abuasab, S. F. Mohadam, H. Hwang, X. Wang, K. Sasaki, M. Yilmaz, T. Kadia, C. DiNardo, N. Daver, N. Pemmaraju, G. Borthakur, F. Ravandi, G. Garcia-Manero, K. Takahashi
Journal: HemaSphere (2022)

Background: Inflammatory Bowel Disease (IBD) comprises two major disorders: ulcerative colitis (UC) and Crohn’s disease (CD). Patients (pts) with IBD are at an increased risk of cancer secondary to long-standing intestinal inflammation and secondary to immunosuppressive therapies, including but not limited to colorectal cancer, hepatobiliary tract cancer, Hodgkin, and non-Hodgkin lymphomas. However, very little data is available regarding the risk of secondary myeloid neoplasm (MNs) in pts with IBD except for the well-known association between azathioprine with therapy related MNs. Aims: To describe the clinical characteristics of secondary MNs in patients with IBDs. Methods: Retrospective chart review of patients with MNs who were previously treated for IBDs was performed. A descriptive statistic was performed to define the demographics, clinical and biological characteristics of the pts included in the study. Results: Between 2012 and 2020, 43 pts were identified to have developed a secondary MN during or after the treatment of IBDs. Sixty-three percent (27/43) were female, and 37% (16/43) were male, with most of the pts being of white ethnicity (35/43, 81%). Seventy percent (30/43) of the secondary MNs arose after the therapy for CD, whereas 30% (13/43) arose after UC therapy. The median age at the time of MN diagnosis was 59 years (yrs) (range, 23-83) and latency from IBD diagnosis was 16 years (range, 0-56). Twenty-five pts were on active treatment for IBD at the time of MN diagnosis (9 on biological agent, 11 on mesalamine, and 2 on azathioprine), whereas 18 were in remission. In addition, 8 pts (19%) had secondary cancer before the MN diagnosis (2 pts lymphoma, 2 pts skin cancer, ovary Ca, uterine Ca, schwannoma, and adrenal tumor) and 3 of them received therapy (chemotherapy and/or radiation therapy). Seventy four percent (32/43) of MN diagnoses were Acute myeloid leukemia (AML), 9 (21%) pts had myelodysplastic syndrome (MDS), and one each for MDS/myeloproliferative neoplasm (MPN) and chronic myelomonocytic (CMML). Seventy percent of the patients had cytogenetic abnormalities:13 pts (30%) with complex karyotype and 6 pts (14%) with core-binding factor (CBF) abnormalities (5 with inv16 and 1 with t [8;21]). The most common somatic mutations included: TP53 (N = 10, 23%), FLT3 (N = 7, 16%), RAS (N = 8, 19%), TET2 (N = 7, 16%), and DNMT3A mutations (N = 6, 14%). Interestingly, all the pts with CBF-AML had prior history of CD, two of them treated with anti TNF-α treatment. The median overall survival (OS) was 2.17 yrs for the whole cohort, and there was no difference in OS between MNs arose from CD and UC (2.35 and 2.08 yrs for CD and UC, respectively). Seventeen patients underwent allogenic stem cell transplantation, which resulted in remission of IBDs in 13 pts (76%). Image:Summary/Conclusion: We described the clinical characteristics of secondary MNs after IBD therapy. Secondary MNs after IBD therapy included higher than expected prevalence of core-binding factor AML, which was strongly associated with prior history of CD. This observation raises an important question about the association between CD and CBF-AML. Of interest, allogeneic stem cell transplantation led to remission of both MNs and IBDs, highlighting the role of allo SCT in autoimmune diseases.